Powderous formulations of organic acid amides having an aromatic ring system

ABSTRACT

The present invention relates to improved powderous formulations comprising organic acid amides having an aromatic ring system as well as to the production of such formulations.

This application is the U.S. national phase of International Application No. PCT/EP2014/066031 filed 25 Jul. 2014 which designated the U.S. and claims priority to EP 13178142.9 filed 26 Jul. 2013, the entire contents of each of which are hereby incorporated by reference.

The present invention relates to improved powderous formulations comprising organic acid amides having an aromatic ring system as well as to the production of such formulations.

Powderous formulations of organic acid amides having an aromatic ring system are very common and useful formulations. They can then be incorporated in any kind of product wherein such an acid amide is needed.

An example of such an organic acid amide is nicotinamide.

Nicotinamide, which is the amide of nicotinic acid (also known as vitamin B3, niacin and vitamin PP) is an essential human nutrient.

When these organic acid amides are used in a powder form, these formulations do unfortunately have a tendency to explode.

Even when the powder has a prominent amount of larger particles, there is always a certain amount of small particles present. These small particles are responsible for the explosion risk.

Dust explosions are a huge risk in any processes wherein powders are used. Therefore there is a need for powderous formulations with low explosion hazard. But nevertheless the powderous formulations must still have the essential (and advantageous) features of a powder, such as free flowable, easy to transport, easy to dosage etc.

It is known from the prior art that certain auxiliary compounds and carrier material, can minimize the explosion risk of powderous formulation comprising vitamin E.

Due to the importance of such non-explosive formulations, there is always a need for improved formulation.

Surprisingly, it was found out that formulations with a very high active ingredient content of 65 weight-% (wt-%) and more, based on the total weight of the powderous formulation can be provided. Furthermore there is no need for a carrier material.

It was found that powderous formulations comprising

65-95 wt-%, based on the total weight of the powderous formulation, of at least one compound of formula (I)

wherein X is —N— or —CH— and R¹ is H or a C₁-C₄ alkyl moiety, and R² is H or a C₁-C₄ alkyl moiety, and comprising one or more specific compounds (auxiliary compound), do have a low risk of explosion.

Therefore the present application relates to powderous formulations (I) comprising

-   -   (i) 65-95 wt-%, based on the total weight of the powderous         formulation, of at least one compound of formula (I)

-   -   -   wherein         -   X is —N— or —CH— and         -   R¹ is H or a C₁-C₄ alkyl moiety, and         -   R² is H or a C₁-C₄ alkyl moiety, and

    -   (ii) 5-35 wt-%, based on the total weight of the powderous         formulation, of at least one auxiliary compound selected from         the group consisting of aluminum ammonium sulphate, aluminum         potassium sulfate, ammonium acetate, ammonium bisulphite,         ammonium carbonate, ammonium chloride, ammonium dihydrogen         phosphate, ammonium hydrogen carbonate, bentonite,         montmorillonite, calcium aluminates, calcium carbonate, calcium         silicate, synthetic calcium sulphate dihydrate, calcium sulfate,         kaolinitic clays (such as Kaolin), diatomaceous earth, perlite,         potassium bisulphite, potassium hydrogen carbonate, potassium         sulphate, potassium carbonate, sepiolitic clays, silicic acid,         synthetic sodium aluminosilicate, sodium aluminosulfate, sodium         bisulphate, sodium carbonate, sodium chloride, sodium hydrogen         carbonate, sodium sulphate, vermiculite, calcium carbonate,         magnesium carbonate, calcareous marine algae, magnesium oxide,         magnesium sulphate, dicalcium phosphate, tri-calcium phosphate,         mono-dicalcium phosphate, defluorinated rock-phosphate,         monocalcium phosphate, calcium-magnesium phosphate,         mono-ammonium phosphate, magnesium phosphate,         sodium-calcium-magnesium phosphate, mono-sodium phosphate,         glycerol, propylene glycol (E 1520), glyceryl triacetate         (E1518), sorbitol (E420), polydextrose, lactic acid and urea.

Preferably, R¹ in the definition of formula (I) is H, CH₃, CH₂CH₃, (CH₂)₂CH₃ and (CH₂)₃CH₃. More preferably R¹ is H or CH₃.

Preferably, R² in the definition of formula (I) is H, CH₃, CH₂CH₃, (CH₂)₂CH₃ and (CH₂)₃CH₃. More preferably R² is H or CH₃.

Preferably X is N.

Therefore the present invention relates to a powderous formulation (I′), which is formulation (I) wherein R¹ in the definition of formula (I) is H, CH₃, CH₂CH₃, (CH₂)₂CH₃ and (CH₂) CH₃ (preferably H or CH₃) and wherein R² in the definition of formula (I) is H, CH₃, CH₂CH₃, (CH₂)₂CH₃ and (CH₂)₃CH₃ (preferably H or CH₃) and wherein X in the definition of formula (I) is N.

It is clear that the sum of all the wt-%'s always add up to 100.

In the context of the present invention the specific compounds (ii) are also defined as auxiliary compounds.

Compounds of formula (Ia) are preferred

Therefore the present invention relates to a powderous formulation (II), which is formulation (I) or (I′), wherein at least one compound of formula (Ia) is used.

More preferred is the compound of formula (Ia),

which is nicotinamide.

Therefore the present invention relates to a powderous formulation (III), which is formulation (I), (I′) or (II), wherein the compound of formula (Ia′) is used.

Preferably, the auxiliary compounds have an average particle size (d 0.5) (in the powderous formulation) of 10 μm-100 μm.

Furthermore preferred are formulations (IV), which are formulations (I), (I′), (II) or (III), wherein the auxiliary compound has an average particle size (d 0.5) of 10 μm-100 μm.

The average particle sizes are measured by a Malvern Master Sizer 2000. During this laser diffraction measurement, particles are passed through a focused laser beam. These particles scatter light at an angle that is inversely proportional to their size. The angular intensity of the scattered light is then measured by a series of photosensitive detectors. The map of scattering intensity versus angle is the primary source of information used to calculate the particle size. For the measurement of dry materials such as the applied additives, a dry powder feeder (Malvern Scirocco) was used.

The explosion hazard of powders (dusts) is usually measured by a standardized method (EN 13821:2002 (Determination of minimum ignition energy of dust/air mixtures)). This is the method which is used for the determination of all MIE values in this patent application. This method allows to determining the minimum ignition energy (MIE) of a powder. The MIE is the minimum amount of energy required to ignite a combustible vapor, gas or dust cloud, for example due to an electrostatic discharge. MIE is measured in joules (J).

The average size of the powder particles for the measurement according to the procedure in EN 13821:2002 is ≦63 μm.

All the MIE values in this patent application are determined by using a modified Hartmann tube (type MIKE 3) available from Adolf Kühner AG (Birsfelden, CH). This equipment is specially designed to allow the measurement of very low ignition energies. This is achieved by having different capacitors installed. The capacitors are designed to store the energy of 1 mJ, 3 mJ, 10 mJ, 30 mJ, 100 mJ, 300 mJ and 1000 mJ.

When measuring the MIE of commercially available powderous formulations comprising at least one compound of formula (I), they are usually in the range of 1-3 mJ. This means that a very low amount of energy is sufficient to initiate an explosion.

On the other hand, the formulations according to the present invention have MIE values in the range of 10-100 mJ.

Therefore the present invention relates to formulations (V), which are formulations (I), (I′), (II), (III) or (IV) with MIE values of 10-100 mJ (determined by the method of EN 13821:2002).

The formulations according to the present invention are dry powders. But depending on the process of production as well as the storage conditions, the formulations can comprise some water. The water content is usually below 5 wt-%, based on the total weight of the formulation.

Therefore a further embodiment of the present invention relates to formulations (VI), which are formulations (I), (I′), (II), (III), (IV) or (V), wherein 0-5 wt-%, based on the total weight of the formulation, of water is present.

The compounds of formula (I) can be from a natural source or they can be synthesised. Due to the nature of either the isolation process or the process of production, it is possible that traces of side products are present.

Optionally a carrier material can be used in the powderous formulation according to the present invention.

The optional carrier material used in the formulations according to the present invention are commonly known and used carrier material. A suitable carrier material is synthetically produced precipitated silica or formiate (such as calcium formiate). This carrier material consists of porous particles. Other suitable carrier materials are proteins, starches, lignosulfonates and gums.

Preferably the powderous formulations do not comprise other ingredients/compounds than those as disclosed above. They do not contain any commonly used stabilisers, carrier material, surface active ingredients or sugars.

Preferred formulations of the present invention are formulations (VII), which are formulations (I), (I′), (II), (III), (IV), (V) or (VI) comprising

-   (ii) 5-35 wt-%, (preferably 10-30 wt-%), based on the total weight     of the formulation, of at least one compound selected from the group     consisting of ammonium dihydrogen phosphate, (purified) diatomaceous     earth, potassium hydrogen carbonate, potassium sulphate, potassium     carbonate, sodium chloride and sodium hydrogen carbonate.

More preferred are formulations (VII′), which are formulations (VII) with MIE values of 10-100 mJ (determined by the method of EN 13821:2002).

Furthermore preferred are formulations (VII′), which are formulations (VII′) wherein the auxiliary compound has an average particle size (d 0.5) of 10 μm-100 μm.

As disclosed above, an advantage of the present formulation is—besides the high amount of the acid amide—that it can consist of one or more acid amides and one or more auxiliary compound (and eventually some water).

An especially preferred embodiment of the present invention relates to formulations (VIII), consisting of

-   (i) 70-90 wt-%, based on the total weight of the powderous     formulation, of at least one compound of formula (Ia)

-   (ii) 10-30 wt-%, based on the total weight of the powderous     formulation, of at least one auxiliary compound selected from the     group consisting of ammonium dihydrogen phosphate, (purified)     diatomaceous earth, potassium hydrogen carbonate, potassium     sulphate, potassium carbonate, sodium chloride, sodium sulphate and     sodium hydrogen carbonate, and -   0-5 wt-%, based on the total weight of the powderous formulation, of     water.

A very especially preferred embodiment of the present invention relates to formulations (IX), consisting of

-   (i) 70-90 wt-%, based on the total weight of the powderous     formulation, of

-   (ii) 10-30 wt-%, based on the total weight of the powderous     formulation, of sodium chloride, and -   0-5 wt-%, based on the total weight of the powderous formulation, of     water.

To produce a powder according to the present invention (formulations (I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX)) the at least one compound of formula (I) is blended with at least one auxiliary compound. This process can be carried out by using any usually used blenders. The sequence of adding the compounds is not essential for the invention.

All the above disclosed formulations (I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX) can be used as such or in food products, feed products and personal care products.

Furthermore, the present invention relates to a process of production of food products, feed products and personal care products using at least one formulation (I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX).

All the above disclosed formulations (I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX) can be used as such in the production of food products, feed products and personal care products.

Furthermore the invention also relates to food products, feed products and personal care products comprising at least one formulations (I), (I′), (II), (III), (IV), (IV′), (IV″), (V), (VI), (VII), VII′), (VII″), (VIII) and/or (IX).

The invention is illustrated by the following Examples. All temperatures are given in ° C. and all parts and percentages are related to the weight.

EXAMPLES Example 1

850 g nicotinamide (Rovimix® Nicotinamide from DSM) (purity 99.5%) was filled into an appropriate blender (Turbula) and 150 g sodium chloride having a particle size, analysed by laser diffraction, of 54 μm was added, the mix then blended for 10 minutes. The material was then transferred to a Retsch Grindomixer and milled (10′000 rpm/1 min.). The median size of this material was 31 μm. The obtained white powder was filled into a container.

The powder was analysed according to the above mentioned EN 13821:2002 and the minimum ignition energy was found to be 10-30 mJ.

Example 2

750 g nicotinamide (Rovimix® Nicotinamide from DSM) (purity 99.5%) was filled into an appropriate blender (Turbula) and 250 g sodium chloride having a particle size, analysed by laser diffraction, of 54 μm was added, the mix then blended for 10 minutes. The material was then transferred to a Retsch Grindomixer and milled (10′000 rpm/1 min.). The median size of this material was 30 μm. The obtained white powder was filled into a container.

The powder was analysed according to the above mentioned EN 13821:2002 and the minimum ignition energy was found to be 30-100 mJ. 

The invention claimed is:
 1. A powderous formulation comprising: (i) 70-90 wt-%, based on the total weight of the powderous formulation, of at least one compound of formula (I):

 wherein X is —N—; and each of R¹ and R² is H, CH₃, CH₂CH₃, (CH₂)₂CH₃ or (CH₂)₃CH₃; and (ii) 10-30 wt-%) based on the total weight of the powderous formulation, of at least one auxiliary compound selected from the group consisting of ammonium dihydrogen phosphate, purified diatomaceous earth, potassium hydrogen carbonate, potassium sulphate, potassium carbonate, sodium chloride and sodium hydrogen carbonate, wherein the powderous formulation has a minimum ignition energy (MIE) value of 10 mJ or greater.
 2. The powderous formulation according to claim 1, wherein each of R¹ and R² is H or CH₃.
 3. The powderous formulation according to claim 1, wherein the compound of formula (I) is a compound of formula (Ia):


4. The powderous formulation according to claim 1, wherein the compound of formula (I) is a compound of formula (Ia′):


5. The powderous formulation according to claim 1, wherein the auxiliary compound has an average particle size (d 0.5) of 10 μm-100 μm.
 6. The powderous formulation according to claim 1, having MIE values of 10-100 mJ as determined by EN 13821:2002.
 7. The powderous formulation according to claim 1, wherein the formulation further comprises 0-5 wt-%, based on the total weight of the formulation, of water is present.
 8. The powderous formulation according to claim 1, which further comprise a carrier material selected from the group consisting of synthetically produced precipitated silicas, synthetically produced precipitated formates, proteins, starches, lignosulfonates and gums.
 9. The powderous formulation according to claim 1, consisting of: (i) 70-90 wt-%, based on the total weight of the powderous formulation, of a compound according to formula (Ia):

(ii) 10-30 wt-%, based on the total weight of the powderous formulation, of the at least one auxiliary compound, and (iii) 0-5 wt-%, based on the total weight of the powderous formulation, of water.
 10. The powderous formulation according to claim 6, having a MIE of 30-100 mJ.
 11. Food products, feed products and personal care products comprising the powderous formulation according to claim
 1. 